Cocaine addiction is the obsessive or uncontrollable abuse of cocaine. Cognitive Behavioral Therapy (CBT) shows promising results. Spiritual based Twelve-step programs such as Cocaine Anonymous (modeled on Alcoholics Anonymous) have some success combatting this problem. A cocaine vaccine is also being tested which may prevent the recipient from feeling the desirable effects of the drug, although a similar effort to develop a heroin vaccine was abandoned as ineffective in the 1970s. Cocaine has positive reinforcement effects, which refers to the effect that certain stimuli have on behavior. Good feelings become associated with the drug, causing a frequent user to take the drug as a response to bad news or mild depression. This activation strengthens the response that was just made. If the drug was taken by a fast acting route such as injection or inhalation, the response will be the act of taking more cocaine, so the response will be reinforced. Powder cocaine, being a club drug is most commonly available in the evening and night hours. Since cocaine is a stimulant, a user will often drink large amounts of alcohol during and after usage or smoke marijuana to dull the effects to help one achieve slumber. These several hours of temporary relief and pleasure will further reinforce the positive response. Other downers such as heroin and various pharmaceuticals are often used for the same purpose, further increasing addiction potential and harmfulness. It is speculated that cocaine's addictive properties stem from its DAT-blocking effects (in particular, increasing the dopaminergic transmission from ventral tegmental area neurons). However, a study has shown that mice with no dopamine transporters still exhibit the rewarding effects of cocaine administration . Later work demonstrated that a combined DAT/SERT knockout eliminated the rewarding effects. The rewarding effects of cocaine are influenced by circadian rhythms, possibly by involving a set of genes termed "clock genes". Cocaine - Treatment Studies have shown that gamma vinyl-gamma-aminobutyric acid (gamma vinyl-GABA, or GVG), a drug normally used to treat epilepsy, blocks cocaine's action in the brains of primates. GVG increases the amount of the neurotransmitter GABA in the brain and reduces the level of dopamine in the region of the brain which is thought to be involved in addiction. In January 2005 the US Food and Drug Administration gave permission for a Phase I clinical trial of GVG for the treatment of addiction. Another drug currently tested for anti-addictive properties is the cannabinoid antagonist rimonabant. GBR 12909 (Vanoxerine) is a selective dopamine uptake inhibitor. Because of this, it reduces cocaine's effect on the brain, and may help to treat cocaine addiction. Studies have shown that GBR, when given to primates, suppresses cocaine self-administration. Venlafaxine (Effexor), although not a dopamine re-uptake inhibitor, is a potent serotonin-norepinephrine reuptake inhibitor which has been successfully used to combat the depression caused by cocaine and to a lesser extent, the addiction associated with the drug itself. Venlafaxine has been shown to have significant withdrawal problems itself, and can lead to lifetime use due to these withdrawal effects. A statistically significant number of people prescribed Effexor have committed suicide (2 attempts per 1000 patients, vs 156 suicides per 1000 untreated depressives).